PUBLICATION
Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects
- Authors
- Eimon, P.M., Ghannad-Rezaie, M., De Rienzo, G., Allalou, A., Wu, Y., Gao, M., Roy, A., Skolnick, J., Yanik, M.F.
- ID
- ZDB-PUB-180118-2
- Date
- 2018
- Source
- Nature communications 9: 219 (Journal)
- Registered Authors
- De Rienzo, Gianluca, Yanik, Mehmet Faith
- Keywords
- none
- MeSH Terms
-
- Disease Models, Animal
- Electrophysiological Phenomena*
- Epilepsies, Myoclonic/diagnosis
- Epilepsies, Myoclonic/physiopathology
- Brain/physiopathology*
- Larva/drug effects
- Larva/genetics
- Larva/physiology
- Humans
- Zebrafish/genetics
- Zebrafish/physiology*
- Animals
- Electrophysiology/methods
- Psychotropic Drugs/pharmacology*
- Psychotropic Drugs/toxicity
- PubMed
- 29335539 Full text @ Nat. Commun.
Citation
Eimon, P.M., Ghannad-Rezaie, M., De Rienzo, G., Allalou, A., Wu, Y., Gao, M., Roy, A., Skolnick, J., Yanik, M.F. (2018) Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects. Nature communications. 9:219.
Abstract
Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson's disease. To determine whether drugs that enhance BAP complexity produces positive outcomes, we used light pulses to trigger seizures in a model of Dravet syndrome, an intractable genetic epilepsy. The highest-ranked compounds identified by BAP analysis exhibit far greater anti-seizure efficacy and fewer side effects during subsequent in-depth behavioral assessment. This high correlation with behavioral outcomes illustrates the power of brain activity pattern-based screens and identifies novel therapeutic candidates with minimal side effects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping